WEI Daoyan,DAI Bingbing,WANG Zhonghe,et al.Adenovirus-mediated IL-12 gene therapy in combination with radiotherapy for murine liver cancer[J].Chinese Journal of Radiological Medicine and Protection,2001,21(4):279-281
Adenovirus-mediated IL-12 gene therapy in combination with radiotherapy for murine liver cancer
Received:January 05, 2001  
DOI:
KeyWords:Liver cancer  Adenovirus  Interleukin-12  Gene therapy  Radiotherapy
FundProject:国家863高技术计划基金资助项目(863012452);国家自然科学重点课题基金资助项目(39710440)
Author NameAffiliation
WEI Daoyan Department of Biochemistry &
Research Center for Human Gene Therapy, Shanghai Second Medical University, Shanghai 200025, China 
DAI Bingbing Department of Biochemistry &
Research Center for Human Gene Therapy, Shanghai Second Medical University, Shanghai 200025, China 
WANG Zhonghe 上海第九人民医院放疗科 
陈诗书 Department of Biochemistry &
Research Center for Human Gene Therapy, Shanghai Second Medical University, Shanghai 200025, China 
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Abstract::
      Objective To investigate the synergistic antitumor effects of adenovirus mediated IL-12 gene therapy in combination with radiotherapy in mice bearing liver cancer. Methods Balb/c mice bearing liver cancer received the treatment at day 1 with tumor local irradiation (TLI) of 20 Gy or mask irradiation when tumor size reached 0.6-1.0 cm. Within 1 hour after irradiation,adenovirus containing IL-12 gene or PBS was intratumorally injected once a week. Forty-eight hours after the second injection,IFN-γ levels in sera and the supernatant of cultured spleen cells were assayed by ELISA, CTL activity of spleen cells was measured by 3H-TdR release assay,and phenotypes of tumor infiltrating lymphocytes were analysed by immunohistochemical staining. Results The growth of tumors in animals treated with a combination of IL-12 gene therapy and TLI was inhibited more significantly than those with either single treatment (P <0.01).Tumors of about 50% mice with the combined treatment were eradicated and there was no tumor developed after rechallenged with subcutaneous injection of MM45T.Li cells.lmmunohistochemical staining showed that combined treatment of IL-12 gene therapy and TLI could induce abundant CD4+ and CD8+ lymphocyte infiltration and tumor specific cytolytic activities, and the levels of IFN-γ in sera were higher in IL-12 gene therapy and IL-12 gene therapy combined with TLI groups. Conclusion These results suggest that IL-12 gene therapy combined with radiotherapy is more effective than both single treatment modalities and can induce specific antitumor immunoreponse greatly.
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